Published: 2022-02-25

Comparison of combination metformin-vildagliptin versus metformin-glimepiride in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy

Anuradha T. Deshkar, Ujwala P. Gawali


Background: Metformin has been recommended as a first-line therapy for T2DM in many guidelines. Adding a sulfonylurea to metformin has been a conventional and gold standard for decades to achieve tight glycaemic control. dipeptidyl peptidase-4 (DPP-4) inhibitors, an incretin-based therapy has emerged as important adjunctive drugs in T2DM. Therefore, the present study was planned to evaluate and compare the efficacy and safety of combination metformin-vildagliptin and metformin-glimepiride in patients of T2DM inadequately controlled with metformin monotherapy.

Methods: A total 45 patients were allocated to each metformin-vildagliptin group and metformin-glimepiride group. Fasting plasma glucose, post prandial plasma glucose, body weight, adverse events were recorded at 0 week, 6 weeks, and 12 weeks. Glycosylated haemoglobin was recorded at 0 week and 12 weeks.

Results: There was no statistically significant difference between the two groups (p>0.05) at the end of 12 weeks in the mean percentage reduction in FPG, PPPG and HbA1c.There was statistically highly significant (p<0.0001) difference between the two groups in mean percentage change in weight at the end of 12 weeks. Hypoglycemic events were significantly (p<0.05) more in metformin-glimepiride group. There was no statistically significant difference in the incidence of other adverse events between the two groups (p>0.05).

Conclusions: In patients of T2DM with inadequately controlled metformin monotherapy, combination metformin-vildagliptin provides comparable efficacy in terms of FPG, PPPG and HbA1c to that of combination metformin-glimepiride with no risk of weight gain reduction in risk of hypoglycemic events.


Type 2 diabetes mellitus, Metformin-vildagliptin, Metformin-glimeperide, Hypoglycamia

Full Text:



Scheen AJ. Pathophysiology of type 2 diabetes. Acta Clin Belg. 2003;58(6):335-41.

International diabetes federation-facts & figures. Available at: what-is-diabetes/factsfigures.html. Accessed on 20 August 2021.

Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its complications in India. Nat Rev Endocrinol. 2016;12(6):357-70.

India-International Diabetes Federation. Available at: Accessed on 20 August 2021.

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. Ten year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359:1565-76.

Powers AC, D’Alessio D. Endocrine Pancreas and Pharmacotherapy of Diabetes Mellitus and Hypoglycemia. In: Burton LL, editor. Goodman and Gilman’s Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw Hill Education; 2017: 863-86.

Standards of Medical Care in Diabetes. Available at: Standards-of-Care.pdf. Accessed on 20 August 2021.

Global guideline for type 2 diabetes. Available at: Accessed on 20 August 2021.

Papanas N, Maltezis E. Metformin: a review of its use in the treatment of type 2 diabetes. Clin Med Ther. 2009;1:1367-81.

Esposito K, Bellastella G, Giugliano D. When metformin fails in type 2 diabetes mellitus. Arch Intern Med. 2011;171:365-6.

Halimi S, Schweizer A, Minic B, Foley J, Dejager S. Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. Vasc Health Risk Manag. 2008; 4(3):481-92.

Zimmerman BR. Sulfonylureas. Endocrinol Metab Clin North Am. 1997;26:511-21.

Inzucchi SE, Bergenstal RM, Buse JB. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-79.

Balas B, Baig MR, Watson C. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007; 92:1249-55.

Ahren B, Foley JE, Bosi E. Clinical evidence and mechanistic basis for vildagliptin’s action when added to metformin. Diabetes Obes Metab. 2011; 13:193-203.

Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. J Am Stat Assoc. 1991;86(416):1149.

Gupta S, Khajuria V, Tandon V, Mahajan A, Gillani Z. Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study. Perspect Clin Res. 2015;6(3):163.

Jeon HJ, Oh TK. Comparison of vildagliptin-metformin and glimepiridemetformin treatments in type 2 diabetic patients. Diabetes Metab J. 2011; 35:529-35.

Mokta JK, Ramesh, Sahai AK, Kaundal KP, Mokta K. Comparison of safety and efficacy of glimepiride-metformin and vildagliptin-metformin treatment in newly diagnosed type 2 diabetic patients. J Assoc Physicians India. 2018;33:30-5.

To compare the safety and efficacy of glimepiride – metformin with vildagliptin - metformin in type 2 diabetes mellitus patients in a tertiary care hospital. Available at: eprint/4512. Accessed on 20 August 2021.

Ferrannini E, Fonseca V, Zinman B, Matthews D, Ahrén B, Byiers S, et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diabetes Obes Metab. 2009;11:157-66.

Matthews DR, Dejager S, Ahren B, Fonseca V, Ferrannini E, Couturier A, et al. Vildagliptin add. on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: Results from a 2-year study. Diabetes Obes Metab. 2010;12:780-9.

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, SherwinR, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

Ahrén B, Schweizer A, Dejager S, Villhauer EB, Dunning BE, Foley JE. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes Metab. England; 2011; 13(9):775-83.

Boschmann M, Engeli S, Dobberstein K, Budziarek P, Strauss A, Boehnke J, et al. Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients. J Clin Endocrinol Metab. 2009;94(3):846-52.